Ketogenic Diet May Overcome Drug Resistance With PI3K Inhibitors

Researchers have shown in mouse models that using PI3K inhibitor targeted therapy along with a ketogenic diet may help prevent or overcome the drug resistance that can eventually occur. The findings were reported in Nature.

PI3K inhibitors are approved for treatment of leukemia and lymphoma, but they have not seen the same success with solid tumors, partly because of drug resistance. Previous studies have shown that resistance occurs because PI3K inhibitors can increase glucose and therefore insulin levels, which causes cancer cells to override the inhibitor and activate a signaling loop that supports cancer cell survival and growth. A ketogenic diet focuses mainly on fats and protein and limits carbohydrates, which keeps glucose and insulin levels low.

The researchers used pancreatic, bladder, endometrial, and breast cancer tumor models in mice, treating them with PI3K inhibitors and a ketogenic diet simultaneously. The combination treatment increased their response to PI3K inhibitors and reduced tumor growth without causing any additional side effects in the mice.

They also tested just the ketogenic diet in the mice without adding PI3K inhibitors. All tumor models showed variable effects, indicating that the diet alone was “insufficient to cause the tumor response observed” and actually accelerated cancer progression in a mouse model of leukemia.